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Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.

TitleGenome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.
Publication TypeJournal Article
Year of Publication2017
Authorsvan Rooij FJA, Qayyum R, Smith AV, Zhou Y, Trompet S, Tanaka T, Keller MF, Chang L-C, Schmidt H, Yang M-L, Chen M-H, Hayes J, Johnson AD, Yanek LR, Mueller C, Lange L, Floyd JS, Ghanbari M, Zonderman AB, J Jukema W, Hofman A, van Duijn CM, Desch KC, Saba Y, Ozel AB, Snively BM, Wu J-Y, Schmidt R, Fornage M, Klein RJ, Fox CS, Matsuda K, Kamatani N, Wild PS, Stott DJ, Ford I, P Slagboom E, Yang J, Chu AY, Lambert AJ, Uitterlinden AG, Franco OH, Hofer E, Ginsburg D, Hu B, Keating B, Schick UM, Brody JA, Li JZ, Chen Z, Zeller T, Guralnik JM, Chasman DI, Peters LL, Kubo M, Becker DM, Li J, Eiriksdottir G, Rotter JI, Levy D, Grossmann V, Patel KV, Chen C-H, Ridker PM, Tang H, Launer LJ, Rice KM, Li-Gao R, Ferrucci L, Evans MK, Choudhuri A, Trompouki E, Abraham BJ, Yang S, Takahashi A, Kamatani Y, Kooperberg C, Harris TB, Jee SHa, Coresh JJ, Tsai F-J, Longo DL, Chen Y-T, Felix JF, Yang Q, Psaty BM, Boerwinkle E, Becker LC, Mook-Kanamori DO, Wilson JG, Gudnason V, O'Donnell CJ, Dehghan A, L Cupples A, Nalls MA, Morris AP, Okada Y, Reiner AP, Zon LI
Secondary AuthorsGanesh SK
Corporate AuthorsBioBank Japan Project
JournalAm J Hum Genet
Volume100
Issue1
Pagination51-63
Date Published2017 Jan 05
ISSN1537-6605
KeywordsAfrica, Alleles, Animals, Bayes Theorem, Continental Population Groups, Erythrocytes, Erythropoiesis, Ethnic Groups, Europe, Far East, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, RNA-Binding Proteins, Zebrafish
Abstract

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong inĀ vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

DOI10.1016/j.ajhg.2016.11.016
Alternate JournalAm J Hum Genet
PubMed ID28017375
PubMed Central IDPMC5223059
Grant ListR01 HL122684 / HL / NHLBI NIH HHS / United States
P30 CA034196 / CA / NCI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 HL039693 / HL / NHLBI NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
P01 HL032262 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL048801 / HL / NHLBI NIH HHS / United States
U54 DK110805 / DK / NIDDK NIH HHS / United States
R01 HL112642 / HL / NHLBI NIH HHS / United States
U54 DK106829 / DK / NIDDK NIH HHS / United States